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81.
Microvascular structural entropy: A novel approach to assess angiogenesis in pituitary tumors 总被引:2,自引:0,他引:2
Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify
regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas
and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to
determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1
labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic
parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences
in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing
adenomas 1.5±0.27; carcinomas 15.0±4.04) and MVD (PRL-producing adenomas 2.7±0.34; carcinomas 4.2±0.72), the MSE values were
significantly higher in adenomas (171.5±25.37) than in carcinomas (67.9±17.45). These results indicate that PRL-producing
carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between,
microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling
index (r=0.511, p=0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity
in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding
of the role of microvasculature in pituitary tumor progression. 相似文献
82.
Salmena L Lemmers B Hakem A Matysiak-Zablocki E Murakami K Au PY Berry DM Tamblyn L Shehabeldin A Migon E Wakeham A Bouchard D Yeh WC McGlade JC Ohashi PS Hakem R 《Genes & development》2003,17(7):883-895
Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency. 相似文献
83.
Chorioallantoic membrane angiogenesis model for tissue engineering: a new twist on a classic model 总被引:4,自引:0,他引:4
Tissue-engineering (TE) applications include the isolation, culture, and seeding of cells into a suitable matrix or scaffold before in vivo transplantation. After transplantation, vascularization of the scaffold is a principal limiting factor for cell viability for the first 6-8 days posttransplantation. A model for systematic analysis of this process has been developed. Fertilized White Leghorn eggs were incubated (at 37.8 degrees C in 60% relative humidity) and opened on day 3 of incubation. Preadipocyte-seeded fibrin constructs were implanted in a specially designed plastic cylinder and placed through the opening on the surface of the chorioallantoic membrane (CAM) on day 8 of incubation. Vascularization of the constructs by chorioallantoic blood vessels was assessed for up to 8 days posttransplantation. The survival rate for embryos receiving transplanted constructs was about 90%. Histology confirmed transplant cell viability at day 4 posttransplantation and vascularization of the constructs by avian endothelial cells began at this time. A new in vivo model to study the effect of angiogenesis in TE constructs, including assessments of viability, proliferation, and differentiation of transplanted cells and biomaterial properties, is presented. Advantages include easy access to the vascular network of the CAM, lack of immunocompetence, low costs, and avoidance of animal experiments. 相似文献
84.
Jens Wrammert Eva K?llberg William W Agace Tomas Leanderson 《European journal of immunology》2002,32(1):97-103
Plasma cell differentiation is induced in vitro by lipopolysaccharide (LPS) stimulation but can be blocked by including anti-CD40 antibodies. Using subtractive cDNA hybridization we have identified the cell surface protein Ly6C as differentially expressed on B cells stimulated with LPS only. Ly6C has been shown to be expressed on certain T cell subsets and on subsets of macrophages and NK cells, but not on resting B cells. We show that Ly6C is up-regulated upon LPS stimulation of B cells in vitro and that this up-regulation is blocked by anti-CD40 or anti-Ig antibodies. Furthermore, ELISPOT analysis of cells sorted by magnetic-activated cell sorting show that Ly6C is expressed on ex vivo plasma cells from the spleen and bone marrow. Flow cytometric analysis showed that Ly6C is expressed on splenic plasma cells as well as on lamina propria plasma cells. Finally, Ly6C cross-linking positively up-regulated the amount of immunoglobulin produced by LPS-stimulated splenic B cells in vitro. 相似文献
85.
Valles S Caunt CJ Walker MH Qwarnstrom EE 《Laboratory investigation; a journal of technical methods and pathology》2002,82(7):855-862
This study shows that increase in IL-1 receptor levels by platelet derived growth factor (PDGF) involves an enhancement of a matrix-dependent, low-affinity receptor that constitutes a heparan sulfate. Fibronectin attachment caused pronounced alterations in IL-1 receptor function in smooth muscle cells, involving a pronounced increase in cell surface binding from an average of 2,000 up to approximately 8,000 receptors/cell and an increase in affinity (K(a)) of the type I receptor from 1.8 +/- 0.9 x 10(9) to 3.7 +/- 0.5 x 10(9) M(-1). PDGF stimulation similarly enhanced the level of cell surface binding by between 30% and 100%, with, in general, less effect on cells plated on fibronectin. Further, PDGF had a pronounced effect on the type I receptor affinity in the absence of matrix attachment, increasing the K(a) from 1.77 +/- 0.93 x 10(9) to 5.1 +/- 2.1 x 10(9) M(-1). Scatchard analyses revealed that PDGF, similarly to fibronectin attachment, caused enhancement of a second low-affinity binding site. Antibody blocking showed that approximately 50% of the attachment-induced increase was independent of type I receptor binding. Further, a similar fraction of the cell surface interaction was blocked by soluble heparan sulfate and dependent on cell binding to the heparan binding site. Cross-linking demonstrated that, in addition to the type I receptor, IL-1 bound to a second high molecular weight complex of 300 kd, induced by fibronectin attachment as well as by PDGF in the absence of matrix. Biochemical analyses demonstrated that this second site constitutes a heparan sulfate, which directly interacted with the type I receptor after recruitment to the complex, and which bound up to 50% and 25% of the ligand after fibronectin attachment and PDGF stimulation, respectively. The data show that PDGF induces an attachment-regulated low-affinity IL-1 binding site in smooth muscle cells, constituting a heparan sulfate. Correlation of the recruitment of this component to the IL-1 receptor complex with structural regulation of receptor function and enhancement of IL-1-mediated responses suggests that this is a significant mechanism in PDGF augmentation of local inflammatory responses during vessel wall pathogenesis. 相似文献
86.
Numerical chromosomal aberrations in prostate cancer: correlation with morphology and cell kinetics 总被引:3,自引:0,他引:3
Rolf -Peter Henke Eva Krüger Nebahat Ayhan Dirk Hübner Peter Hammerer 《Virchows Archiv : an international journal of pathology》1993,422(1):61-66
Eleven routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by means of in situ hybridization with nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. Cytogenetic information was correlated with morphology, tumour stage and volume as well as with cell kinetics, the latter being assessed by immunohistochemistry with antibodies raised against the proliferative cell nuclear antigen (PCNA) and against a formalin-resistant epitope of the Ki-67 antigen, MIB 1. In 5 of 11 cases, numerical aberrations of at least one chromosome were found. The cases with normal chromosome numbers were those with the smallest volumes of Gleason grade 4 and/or 5 tumour (mean 0.5 cm3) and represented tumours restricted to the prostate. Tumours with aberrations in the number of detected chromosomes showed advanced stages and large volumes of high-grade tumour (mean 12.5 cm3). All 4 tumours with positive surgical margins were recruited from a group with marked local heterogeneity in chromosome numbers. Immunostaining with MIB 1 and PCNA was most intense in areas of high-grade tumour and was positively correlated with the emergence of chromosomal aberrations. The data suggest that the appearance of numerical chromosomal aberrations in prostate cancer coincides with aggressive tumour behaviour and could be used as an additional prognostic marker.This work is part of E.K.'s doctoral thesis 相似文献
87.
Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma 总被引:13,自引:0,他引:13
Woenckhaus J Steger K Werner E Fenic I Gamerdinger U Dreyer T Stahl U 《The Journal of pathology》2002,196(3):335-342
The regulation of apoptosis in atherosclerosis is not completely defined. The aim of this study was to determine the expression of Bcl-2, Bcl-x, Bax, and Bak in relation to apoptosis in advanced atherosclerotic lesions. In atherectomy (15), endarterectomy (10), and control non-atherosclerotic segments of renal (2) and of coronary and carotid (5) arteries, the extent of apoptosis was determined using TdT dUTP nick end labelling (TUNEL) and nuclear morphology (karyorrhexis/pyknosis) and expression of apoptosis regulators by immunohistochemistry and western blot analysis on paraffin-embedded material. In all specimens, the atherosclerotic involvement was advanced: grade V (n=18) and grade VI (n=7). The apoptotic index was high (mean 30%) in advanced lesions compared with controls (<2%) and smooth muscle cells (SMCs) were the predominant cell type undergoing apoptosis. In all TUNEL-positive apoptotic cells, Bax and Bak were present, while Bcl-x was absent. Bcl-2 was absent in a majority of these cells, but occasional TUNEL-positive cells expressed Bcl-2. In non-apoptotic cells, Bcl-x was present and western blot detected only the long isoform, Bcl-xL, from the plaques. In conclusion, increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. Bcl-xL in non-apoptotic cells appears to contribute to prolonged cell survival. 相似文献
88.
The glutathione S-transferase from Plasmodium falciparum 总被引:3,自引:0,他引:3
89.
90.
The case of a retarded child with trisomy of the short arm of chromosome 8 associated with translocation between the short arm of chromosome 8 and the long arm of chromosome 22 is reported. Balanced translocation involving the same chromosomes was present in the mother and brother of the propositus. The specific chromosomes involved in the abnormality in this family were identified by use of fluorescence microscopy with quinacrine mustard staining, autoradiography and Giemsa banding. This appears to be the first case report of this anomaly, although trisomy of the short arm of chromosome 9 has been reported previously. 相似文献